Human INO80 Chromatin Remodeling Complex Regulated Genes And Gene Network Construction

In eukaryotic cells, chromatin structure is in a state of dynamic change: when chromatin structure is tightly compacted, initial transcription factors and RNA polymerase are prevented to access specific sequences of DNA loci and also RNA polymerase is blocked to extend further, then the genes are silenced; and when the chromatin structure is loose, the initial transcription factors and RNA polymerase can access to the promoters, and then the transcription of corresponding genes is active. During the process, Chromatin remodeling complexes are responsible for the change of chromatin structure, and for altering gene transcription. Normally, chromatin remodeling factors can function in the process of gene transcription initiation and are recruited by specific transcription factors to regulate target genes in order to change chromatin structure and also to become a co-active or co-suppressed factors for biological molecular functions.Human Ino80 complex is a conservative ATP-dependent chromatin remodeling complex, belong to the SWI/SNF2 family and plays important roles in a variety of biological processes. As a member of chromatin remodeling complex, hINO80 not only participates in the biological pathways, such as gene regulation, DNA replication, DSB repairing, but also functions in the processes with relation to a lot of important biological functions, such as embryonic development and cell cycle. In the present paper, we focused on the study of hINO80 complex regulated genes, as well as the relationship between the selected hINO80 complex regulated genes. The core subunits Arp8, Ies2, Ies6 and INO80 belonging to HAS domain or insert domain are conservative subunits in the fourteen subunits of human INO80 complex, which are essential in the remodeler function for DNA sliding. In this thesis, we investigated human INO80 complex regulated genes and gene network construction for the regulated genes of human INO80 complex. Firstly, we knocked down the four Ino80 complex’s conservative subunits(Arp8, Ies2, Ies6, INO80) with microRNA interfering method. Then we respectively applied statistical method and GO annotation without statistical analysis to explore the core gene clusters that the complex regulates, including immune response(GO:0051607 defense response to virus)、cell differentiation(GO:0045597: positive regulation of cell differentiation) and carbon and fatty acid metabolism pathways(GO:0006027 glycosamin-oglycan catabolic process and GO:0006633 fatty acid biosynthetic process) and so on. Besides we got twenty high differentially expressed genes that h Ino80 complex may regulate directly, including M160、FAM65B、SIRT4 and LAMP2. From comprehensive understanding of Ino80 downstream genes, we can clearly illustrate the gene regulation network of Human Ino80 complex.